Epigenetic Priming by Hypomethylation Enhances the Immunogenic Potential of Tolinapant in T-cell Lymphoma.

Unlabelled: Programmed cell death mechanisms are important for the regulation of tumor development and progression. Evasion of and resistance to apoptosis are significant factors in tumorigenesis and drug resistance. Bypassing apoptotic pathways and eliciting another form of regulated cell death, namely necroptosis, an immunogenic cell death (ICD), may override apoptotic resistance.

Molecular phylogeny of the threadfin fishes (Polynemidae) using ultraconserved elements.

Threadfins (Teleostei: Polynemidae) are a group of fishes named for their elongated and threadlike pectoral-fin rays. These fishes are commonly found in the world's tropical and subtropical waters, and are an economically important group for people living in these regions, with more than 100,000 t harvested in recent years. However, we do not have a detailed understanding of polynemid evolutionary history such that these fishes can be monitored, managed and conserved as an important tropical food source.

Antagonism of inhibitors of apoptosis proteins reveals a novel, immune response-based therapeutic approach for T-cell lymphoma.

Tolinapant (ASTX660) is a potent, nonpeptidomimetic antagonist of cellular inhibitor of apoptosis proteins 1 and 2 (cIAP1/2) and X-linked IAP, which is currently being evaluated in a phase 2 study in T-cell lymphoma (TCL) patients. Tolinapant has demonstrated evidence of single-agent clinical activity in relapsed/refractory peripheral TCL and cutaneous TCL. To investigate the mechanism of action underlying the single-agent activity observed in the clinic, we have used a comprehensive translational approach integrating in vitro and in vivo models of TCL confirmed by data from human tumor biopsies.

Anatomy and evolution of bioluminescent organs in the slimeheads (Teleostei: Trachichthyidae).

Bacterial bioluminescent organs in fishes have a diverse range of tissues of origin, patterns of compartmentalization, and associated light-conducting structures. The morphology of the perianal, bacterial bioluminescent organ of Aulotrachichthys prosthemius was described previously, but the light organ in other species of slimeheads, family Trachichthyidae, is poorly known. Here, we describe the anatomy of the bioluminescent organs in trachichthyids and places the evolution of this light-producing system in the context of a new phylogeny of the Trachichthyoidei to test the hypothesis that bioluminescence evolved twice in the suborder and that the light-producing component derives from the perianal ectoderm.

The evolution of specialized dentition in the deep-sea lanternfishes (Myctophiformes).

The evolution of heterodonty, the possession of varied tooth morphologies on the jaws of animals, has been relatively unexplored in ray-finned fishes compared to terrestrial vertebrates, and to an even lesser degree in deep-sea fish lineages. Lanternfishes (Myctophiformes) are an abundant and species-rich group endemic to deep-sea pelagic habitats. In this study, we document the presence of heterodonty on the oral jaws of lanternfishes, identifying differing anatomical and positional variations of dentition.

Salamanders and other amphibians are aglow with biofluorescence.

Biofluorescence is the absorption of electromagnetic radiation (light) at one wavelength followed by its reemission at a lower energy and longer wavelength by a living organism. Previous studies have documented the widespread presence of biofluorescence in some animals, including cnidarians, arthropods, and cartilaginous and ray-finned fishes. Many studies on biofluorescence have focused on marine animals (cnidarians, cartilaginous and ray-finned fishes) but we know comparatively little about the presence of biofluorescence in tetrapods.

The first evidence of intrinsic epidermal bioluminescence within ray-finned fishes in the linebelly swallower Pseudoscopelus sagamianus (Chiasmodontidae).

External and histological examination of the photophores of the linebelly swallower Pseudoscopelus sagamianus reveal three epidermal layers of cells that form the light-producing and light-transmitting components of the photophores. Photophores among the examined photophore tracts are not significantly different in structure but the presence of mucous cells in the superficial layers of the photophore suggest continued function of the epidermal photophore in contributing to the mucous coat. This is the first evidence of intrinsic bioluminescence in primarily epidermal photophores reported in ray-finned fishes.

Morphology and evolution of bioluminescent organs in the glowbellies (Percomorpha: Acropomatidae) with comments on the taxonomy and phylogeny of Acropomatiformes.

Bioluminescent organs have evolved many times within teleost fishes and exhibit a wide range of complexity and anatomical derivation. Although some bioluminescent organs have been studied in detail, the morphology of the bacterial light organs in glowbellies (Acropoma) is largely unknown. This study describes the anatomy of the bioluminescent organs in Haneda's Glowbelly (Acropoma hanedai) and the Glowbelly (Acropoma japonicum) and places the evolution of this light-producing system in the context of a new phylogeny of glowbellies and their relatives.

Light in the darkness: New perspective on lanternfish relationships and classification using genomic and morphological data.

Massive parallel sequencing allows scientists to gather DNA sequences composed of millions of base pairs that can be combined into large datasets and analyzed to infer organismal relationships at a genome-wide scale in non-model organisms. Although the use of these large datasets is becoming more widespread, little to no work has been done in estimating phylogenetic relationships using UCEs in deep-sea fishes. Among deep-sea animals, the 257 species of lanternfishes (Myctophiformes) are among the most important open-ocean lineages, representing half of all mesopelagic vertebrate biomass.

A high-resolution mRNA expression time course of embryonic development in zebrafish.

We have produced an mRNA expression time course of zebrafish development across 18 time points from 1 cell to 5 days post-fertilisation sampling individual and pools of embryos. Using poly(A) pulldown stranded RNA-seq and a 3' end transcript counting method we characterise temporal expression profiles of 23,642 genes. We identify temporal and functional transcript co-variance that associates 5024 unnamed genes with distinct developmental time points.

Mirnovo: genome-free prediction of microRNAs from small RNA sequencing data and single-cells using decision forests.

The discovery of microRNAs (miRNAs) remains an important problem, particularly given the growth of high-throughput sequencing, cell sorting and single cell biology. While a large number of miRNAs have already been annotated, there may well be large numbers of miRNAs that are expressed in very particular cell types and remain elusive. Sequencing allows us to quickly and accurately identify the expression of known miRNAs from small RNA-Seq data.

The taxonomic placement of three fossil species and the timing of divergence within the North American topminnows (Teleostei: Fundulidae).

The fossils species †Fundulus detillae, †F. lariversi, and †F. nevadensis from localities in the western United States are represented by well-preserved material with date estimations.

Large-scale analysis of microRNA expression, epi-transcriptomic features and biogenesis.

MicroRNAs are important genetic regulators in both animals and plants. They have a range of functions spanning development, differentiation, growth, metabolism and disease. The advent of next-generation sequencing technologies has made it a relatively straightforward task to detect these molecules and their relative expression via sequencing.

Repeated and Widespread Evolution of Bioluminescence in Marine Fishes.

Bioluminescence is primarily a marine phenomenon with 80% of metazoan bioluminescent genera occurring in the world's oceans. Here we show that bioluminescence has evolved repeatedly and is phylogenetically widespread across ray-finned fishes. We recover 27 independent evolutionary events of bioluminescence, all among marine fish lineages.

Biofluorescence in Catsharks (Scyliorhinidae): Fundamental Description and Relevance for Elasmobranch Visual Ecology.

Biofluorescence has recently been found to be widespread in marine fishes, including sharks. Catsharks, such as the Swell Shark (Cephaloscyllium ventriosum) from the eastern Pacific and the Chain Catshark (Scyliorhinus retifer) from the western Atlantic, are known to exhibit bright green fluorescence. We examined the spectral sensitivity and visual characteristics of these reclusive sharks, while also considering the fluorescent properties of their skin.

The first report of luminescent liver tissue in fishes: evolution and structure of bioluminescent organs in the deep-sea naked barracudinas (Aulopiformes: Lestidiidae).

Bioluminescent organs that provide ventral camouflage are common among fishes in the meso-bathypelagic zones of the deep sea. However, the anatomical structures that have been modified to produce light vary substantially among different groups of fishes. Although the anatomical structure and evolutionary derivation of some of these organs have been well studied, the light organs of the naked barracudinas have received little scientific attention.

Extracellular vesicles from neural stem cells transfer IFN-γ via Ifngr1 to activate Stat1 signaling in target cells.

The idea that stem cell therapies work only via cell replacement is challenged by the observation of consistent intercellular molecule exchange between the graft and the host. Here we defined a mechanism of cellular signaling by which neural stem/precursor cells (NPCs) communicate with the microenvironment via extracellular vesicles (EVs), and we elucidated its molecular signature and function. We observed cytokine-regulated pathways that sort proteins and mRNAs into EVs.

Species-specific bioluminescence facilitates speciation in the deep sea.

The vast darkness of the deep sea is an environment with few obvious genetic isolating barriers, and little is known regarding the macroevolutionary processes that have shaped present-day biodiversity in this habitat. Bioluminescence, the production and emission of light from a living organism through a chemical reaction, is thought to occur in approximately 80 % of the eukaryotic life that inhabits the deep sea (water depth greater than 200 m). In this study, we show, for the first time, that deep-sea fishes that possess species-specific bioluminescent structures (e.

The covert world of fish biofluorescence: a phylogenetically widespread and phenotypically variable phenomenon.

The discovery of fluorescent proteins has revolutionized experimental biology. Whereas the majority of fluorescent proteins have been identified from cnidarians, recently several fluorescent proteins have been isolated across the animal tree of life. Here we show that biofluorescence is not only phylogenetically widespread, but is also phenotypically variable across both cartilaginous and bony fishes, highlighting its evolutionary history and the possibility for discovery of numerous novel fluorescent proteins.

Temporal patterns of diversification across global cichlid biodiversity (Acanthomorpha: Cichlidae).

The contrasting distribution of species diversity across the major lineages of cichlids makes them an ideal group for investigating macroevolutionary processes. In this study, we investigate whether different rates of diversification may explain the disparity in species richness across cichlid lineages globally. We present the most taxonomically robust time-calibrated hypothesis of cichlid evolutionary relationships to date.

Kraken: a set of tools for quality control and analysis of high-throughput sequence data.

New sequencing technologies pose significant challenges in terms of data complexity and magnitude. It is essential that efficient software is developed with performance that scales with this growth in sequence information. Here we present a comprehensive and integrated set of tools for the analysis of data from large scale sequencing experiments.

Exploring power and parameter estimation of the BiSSE method for analyzing species diversification.

Background: There has been a considerable increase in studies investigating rates of diversification and character evolution, with one of the promising techniques being the BiSSE method (binary state speciation and extinction). This study uses simulations under a variety of different sample sizes (number of tips) and asymmetries of rate (speciation, extinction, character change) to determine BiSSE's ability to test hypotheses, and investigate whether the method is susceptible to confounding effects.

Results: We found that the power of the BiSSE method is severely affected by both sample size and high tip ratio bias (one character state dominates among observed tips).

The first record of a trans-oceanic sister-group relationship between obligate vertebrate troglobites.

We show using the most complete phylogeny of one of the most species-rich orders of vertebrates (Gobiiformes), and calibrations from the rich fossil record of teleost fishes, that the genus Typhleotris, endemic to subterranean karst habitats in southwestern Madagascar, is the sister group to Milyeringa, endemic to similar subterranean systems in northwestern Australia. Both groups are eyeless, and our phylogenetic and biogeographic results show that these obligate cave fishes now found on opposite ends of the Indian Ocean (separated by nearly 7,000 km) are each others closest relatives and owe their origins to the break up of the southern supercontinent, Gondwana, at the end of the Cretaceous period. Trans-oceanic sister-group relationships are otherwise unknown between blind, cave-adapted vertebrates and our results provide an extraordinary case of Gondwanan vicariance.